Diagnostic 2-MHz frequency TCD ultrasound is a safe, bedside, repeatable and fast method that can diagnose arterial occlusion, continuously monitor recanalization and may be therapeutic in the setting of thrombolysis. A phase II study carried out within our previous SPOTRIAS grant demonstrated that stroke patients who received 2 hours of continuous TCD ultrasound in addition to rt-PA were significantly more likely to achieve complete recanalization compared to rt-PA alone with no increased risk of brain hemorrhage. Although TCD ultrasound improves recanalization, a definitive efficacy trial aimed at demonstrating improved patient outcomes would require more than 500 patients. To date, only operator-dependent hand-held devices have been shown to be safe and possibly effective. Unfortunately, the lack of widespread availability of trained personnel has limited its application. Development of an operator-independent TCD system would solve this problem and improve enrollment into ultrasound-enhanced stroke clinical trials. Through previous SPOTRIAS funding, such a device was developed at the University of Texas-Houston. The primary specific aim for this pilot phase l/ll study is to determine the safety of a novel, external Hands-Free transcranial Doppler ultrasound system. Importantly, since the Hands-Free TCD ultrasound system will not exceed current energy output standards of FDA approved diagnostic equipment, safety concerns are not anticipated yet will be carefully monitored and evaluated in three distinct groups. Safety and tolerability of the new Hands-Free TCD system, which also uses 2-MHz frequency ultrasound energy, will first be established in healthy volunteers. Safety in these healthy participants will be determined by detailed neurological exams and pre- and post-ultrasound brain MRIs. Next, safety of the device will be evaluated in two different sets of acute ischemic stroke patients: 0-3 hour patients treated with standard IV rt-PA and 3-6 hour non-lytic, image-selected patients treated with sonolysis (ultrasound + microbubbles). Safety in these stroke patients will be measured by incidence of symptomatic intracerebral hemorrhage and adverse events. Our primary hypothesis is that replacing conventional TCD ultrasound hand-held technology with a Hands-Free system will be safe in healthy volunteers as well as acute ischemic stroke patients. Our secondary hypothesis is that Hands-Free TCD will display similar recanalization and early clinical recovery rates compared to available historical diagnostic TCD ultrasound controls exposed to conventional, FDA-approved TCD technology. Data generated during this study will evaluate the safety of replacing an operator-dependent TCD device with an operator-independent system. Our long-term objective is to provide the widespread availability of ultrasoundenhanced thrombolysis which would significantly improve enrollment into ultrasound-stroke trials in order to establish effectiveness of this new treatment. If superior efficacy is established by combining rt-PA and Hands- Free TCD ultrasound, thousands more stroke patients could benefit and recover from their disabling disease.